What we’ve known for 90 years regarding hypothyroidism and angina

What we’ve known for 90 years regarding hypothyroidism and angina … has apparently been forgotten or never introduced to the newer crop of physicians, including cardiologists.

In the past six weeks as I have experienced daily angina pains for the first time in my life, I have met several physicians, including a cardiologist and emergency doctors who, when examining me, have said that it’s not likely my angina symptoms were caused by an increase in T4 dose, despite the twice-repeated coincidence of distressing angina fast following increases in T4 dose. The doctors have sometimes told me that in order to experience thyrotoxicosis that harms the heart, you have to have extremely high T4 values above the lab reference range, which I haven’t got. You can read more about my experience in another post.  But first…

Really?  Is angina only caused by being HYPER-thyroid?  Where did they get this idea…

Yes it can also be caused by T4-therapy in HYPO-thyroid patients, according to the literature.

What we have “known” for 90 years ago about T4-therapy and angina

Way back in 1997 (nearly 20 years ago!) when the article I’m going to analyze was published, there had been “70 years” of knowledge that in hypothyroid patients, angina can be caused or exacerbated by initiating or increasing T4 dose, even slightly:

  • Gammage, M., & Franklyn, J. (1997). Hypothyroidism, thyroxine treatment, and the heart. Heart, 77(3), 189–190.


it is well known that angina and myocardial infarction may be precipitated by the initiation of thyroxine [T4] replacement treatment (even in low dose) in those with underlying coronary artery disease (whether this is evident clinically or electrocardiographically)–

this association was described more than 70 years ago.

This statement was made with such confidence. The writer has cited Toft (1994) and Levine (1961), two articles I’ve cited in my other blog about Thyroid and Angina-like Chest Pain that covers other articles on this theme, some written after 1997.

Has there been any research since 1997 that completely discounted or disproved those previous 70 years of confident knowledge about this? I have not found any articles yet that proves that hypothyroid patients don’t get angina from increases in T4 dose. If you find any, please let me know.

I think it’s more likely that the medical profession has conveniently forgotten this traditional knowledge because nowadays they depend on T4 (thyroxine) as the gold standard of thyroid treatment. They could be embarrassed to admit their favorite drug might cause or worsen the many hypothyroid heart problems it was intended to solve. And they probably think that any research before a certain year is outmoded and untrustworthy because they didn’t have then the fabulous fancy beeping machines and sensitive blood tests we have now.

But back to the article.  There’s more!  Hypothyroid subjects deserve special care of their heart and caution with T4 therapy. The 1997 article writers continue in the next sentence thus:

For this reason, a recent United Kingdom consensus statement for good practice in the management of hypothyroidism recommends that in older patients, especially
those with ischaemic heart disease, the initial dose of thyroxine [T4] should be 25 ug and increased every three to four weeks by 25 ug increments.

Dear writers, I beg of you, why must we only be careful and slow about initiating or raising T4 doses in “older patients” with hypothyroidism and those with already diagnosed heart disease?

What about the many heart problems you have already described as a result of hypothyroidism, without mentioning age or other risk factors?

Under the heading “Cardiovascular effects of untreated hypothyroidism:”

  1. sinus bradycardia … decreases in resting, mean, and maximal heart rates.

  2. An increase in diastolic blood pressure …

  3. an increase in peripheral vascular resistance…

  4. Myocardial contractility is impaired with a reduction in resting left ventricular ejection fraction …

  5. diastolic function may also be impaired, contributing to a reduction in cardiac output, and in a few cases to the development of heart failure.

  6. Pericardial effusions, demonstrated by echocardiography, are frequent in marked thyroid hormone deficiency …

  7. Untreated hypothyroidism is associated with hyperlipidaemia

  8. It is often stated that ischaemic heart disease is more frequent in patients with hypothyroidism …

  9. A necropsy study demonstrated more coronary atherosclerosis in hypertensive hypothyroid patients than in hypertensive euthyroid subjects…

  10. A further necropsy study reported more “severe” coronary atherosclerosisin hypothyroid than euthyroid subjects …

Given these 10 ways they mention that a heart can be harmed by hypothyroidism, wouldn’t you think that initiating T4-therapy should be done with caution in ALL patients who may have been hypothyroid for a long period of time?

Wouldn’t a patient be likely to have a heart “weakened” by long-term hypothyroidism, whether or not a patient is “older” (or otherwise at-risk) or whether or not they’ve already noticed a heart problem (“clinically”) or have been diagnosed (“echocardiographically”) with any heart problems?

Next question I asked of the article:  If it was known for 70 years (as of 1997) that T4 can cause or exacerbate angina, what did they know then about the degree of harm it could do?

Approximately how many hypothyroid people’s hearts may be harmed by T4-therapy?

While it is reported that up to 15% of patients starting thyroxine [T4] therapy will sustain a myocardial infarction within two years, it is also clear that chest pain improves or resolves in up to half of patients with this problem.

Oh, wow, so 15% have a heart attack within 2 years after initiating T-4 therapy!  That’s a little concerning.  (However, maybe you’ll say it’s not because of the T4 therapy, but more likely because of a pre-existing heart condition.)

Yet I also notice that in the sentence above, there’s more doom and gloom, though the authors put the final statement in a positive light, saying “it is also clear that chest pain improves or resolves in up to half of patients with this problem.”

That very same statement also logically means that 50% did not see any improvement or resolution of chest pain after T4-only therapy.

So, if 15% of T4-treated hypothyroid patients are heading for a heart attack and 50% have the prospect of continued chest on T4, how is T4 such a fabulous drug that will cure the ten ills likely to descend upon the hypothyroid heart?

In those 50% + 15% of patients who get worse or see no improvement in heart problems, don’t you have to at least lower the T4 dose to avoid angina and heart attack?

40% of patients with angina are unable to tolerate full replacement doses of thyroxine.

Okay, you do have to lower the dose of T4 if they have angina and it does not go away or gets worse with T4 therapy.

Apparently some hypothyroid patients’ hearts are so weakened by hypothyroidism (or other risk factors) that they can’t tolerate the ideal dose of T4, even if you slowly creep up to the ideal dose as recommended.

So then, is there a logical treatment alternative? since a sufficent dose of T4 is not tolerated by those 40% of patients in whom it exacerbates angina, would you recommend giving them T3 instead of, or in addition to, T4?

There is little evidence that triiodothyronine [T3] treatment is better than thyroxine in patients with ischaemic heart disease, although there is a theoretical benefit should angina worsen and thyroid hormone replacement be stopped because the half life of triiodothyronine [T3] is shorter than that of thyroxine [T4].

What?  You’re going to let a large percentage of hypothyroid patients with angina suffer in a continued hypothyroid state … just because of little evidence that adding T3 to T4, or replacing T4 entirely with T3, might be better for them?

What? If there is a theoretical benefit, why would it not be worth exploring T3 therapy in hypothyroid patients with angina?

And why has it gone completely without mention that prior to the invention and increasing use of synthetic T4 medications in the 1960s, hypothyroid patients were normally treated with dessicated natural thyroid, which included T4, T3, T2, and T1 in various ratios?

And, dear writers, what does that “although” phrase mean at the end of that sentence: “although there is a theoretical benefit should angina worsen and thyroid hormone replacement be stopped because the half life of triiodothyronine [T3] is shorter than that of thyroxine [T4]”?

The sentence seems to reveal deep reluctance to recommend T3, and the convoluted grammar makes the logic of their rationale hard to follow.

  • First of all, it seems you admit a “theoretical benefit” exists for T3, but the benefit exists only theoretically, and only in certain rare or dire circumstances: “should angina worsen and thyroid hormone replacement be stopped.” So, it appears to imply that if angina gets worse for the T4-treated patient, you might have to STOP T4-hormone replacement entirely, not just reduce it to a lower level (the latter would be more likely).  And only in such rare, dire circumstances of having to STOP T4 entirely would you resort to T3 treatment.  Maybe. Theoretically. If it ever happened.
  • What is that final “because” phrase saying, really?  It can’t mean that “thyroid hormone [T4] replacement [must] be stopped because the half-life of triiodothyronine [T3] is shorter than that of thyroxine [T4]” — It can’t mean this because the half life of T3 cannot logically cause one to stop T4 therapy. (If there’s a problem with drug A, it does not make you stop giving drug B.) Therefore, the “because” phrase must attach to the clause earlier in the sentence, thus:

“There is little evidence that triiodothyronine [T3] treatment is better than thyroxine in patients with ischaemic heart disease … because the half-life of triiodothyronine [T3] is shorter than that of thyroxine [T4]”

I’m sorry, but I find it hard to believe that T3 treatment is inferior to T4 treatment in these angina-suffering hypothyroid patients simply because the half-life of T3 is shorter than T4. 

To me, that just means you have to take T3 more frequently than T4 in order to keep its levels constant in the bloodstream.

Don’t you think that a person with angina would happily take T3 several times a day or even in the middle of the night, rather than have heart pain (from too much T4) or have their heart continue in a hypothyroid state (from too little T4)?

Later in the article, the risk of T4-therapy are restated:

The possible effects of thyroxine therapy on cardiac mass and arrhythmia risk raise concerns regarding adverse influences of mild thyroxine excess on cardiac risk.

The authors then debate whether such “concerns” may be reduced by lowered blood cholesterol levels conferred by T4 therapy. However, the article was written at a time when cholesterol’s influence of heart disease risk was unquestioned, and this hypothesis has come under severe criticism in recent years.

In the final paragraph, they also mention a large study that raised concern:

A larger study of 1180 patients treated with thyroxine (about half of whom had low serum thyrotrophin) revealed an increased risk of hospital admission for ischaemic heart disease among those younger than 65 years

But even this study was questioned by mentioning that “half of the subjects included in the study had a previous history of overt hyperthyroidism, which may itself have represented the major risk factor.” What about the other half? Were they treated for a previous history of hypothyroidism?

Why, in an article with the title “Hypothyroidism, thyroxine treatment, and the heart” did the authors lean toward thinking that it was more likely hyper (not hypo, and not the T4-treatment modality itself) that was cause for concern?

Sigh. Let me summarize:

  • As of 1997, experts had known for 70+ years about the way even small doses of T4 can harm a heart already weakened by years of untreated (or perhaps poorly treated) hypothyroidism.
  • They hadn’t yet been able to find a solution to the 15% who suffer MI within 2 years of starting T4-only therapy.
  • They were happy to report that 50% see a decrease in angina on T4-only therapy, even though the other 50% apparently didn’t see an improvement at all.
  • They knew that certain levels of T4-therapy caused worsened angina in 40% of patients with angina.
  • Because of the angina problems, many patients with angina won’t be able to take a “full replacement” dose of T4 that would keep them out of hypothyroidism.
  • These facts above did not shake their firm commitment to T4-only therapy and their deep suspicion of T3 as a possible solution.
  • It appears the mere inconvenience of the shorter half-life of T3 is enough to withhold it from hypothyroid patients with angina that might benefit from it.
  • Strong statements and studies that raise concern over T4 treatment’s ability to harm the heart are quickly questioned and doubted by the authors.

Therefore, even in this article, there are already symptoms of a temptation to forget the 70 previous years of knowledge about T4-treatment causing or worsening heart problems that were likely caused by hypothyroidism.  Could it be that these concerns and beliefs were stated to raise fears that could then be dismissed and replaced with the concern over hyperthyroidism? This is a spectre that may be less challenging for health professionals to deal with, since far fewer thyroid patients are hyperthyroid.


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